tbuckley/cabot-search huggingface dataset:
Reduced Insulin Clearance Differently Relates to Increased Liver Lipid Content and Worse Glycemic Control in Recent-Onset Type 2 and Type 1 Diabetes
Authors: Oana-Patricia Zaharia, Sofia Antoniou, Pavel Bobrov, Yanislava Karusheva, Kálmán Bódis, Yuliya Kupriyanova, Vera Schrauwen-Hinderling, Amalia Gastaldelli, Julia Szendroedi, Robert Wagner, Volker Burkart, Michael Roden, Michael Roden, Hadi Al-Hasani, Bengt Belgardt, Gidon Josia Bönhof, Gerd Geerling, Christian Herder, Andrea Icks, Karin Jandeleit-Dahm, Jörg Kotzka, Oliver Kuß, Eckhard Lammert, Wolfgang Rathmann, Sabrina Schlesinger, Vera Schrauwen-Hinderling, Julia Szendroedi, Sandra Trenkamp, Robert Wagner
Journal: Diabetes Care (2023)

Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in individuals with recent-onset diabetes.Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D) (n = 306), type 2 diabetes (T2D) (n = 489), or normal glucose tolerance (control [CON]) (n = 167) underwent hyperinsulinemic-euglycemic clamps for assessment of whole-body insulin sensitivity (M value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose tolerance tests (ICIVGTT) and mixed-meal tests (ICMMT). Hepatocellular lipid content (HCL) was quantified with 1H-MRS.Both T1D and T2D groups had lower ICCLAMP (0.12 ± 0.07 and 0.21 ± 0.06 vs. 0.28 ± 0.14 arbitrary units [a.u.], respectively, all P < 0.05) and ICMMT (0.71 ± 0.35 and 0.99 ± 0.33 vs. 1.20 ± 0.36 a.u., all P < 0.05) than CON. In T1D, ICCLAMP, ICIVGTT, and ICMMT correlated negatively with HbA1c (all P < 0.05). M value correlated positively with ICIVGTT in CON and T2D (r = 0.199 and r = 0.178, P < 0.05) and with ICMMT in CON (r = 0.176, P < 0.05). HCL negatively associated with ICIVGTT and ICMMT in T2D (r = -0.005 and r = -0.037) and CON (r = -0.127 and r = -0.058, all P < 0.05). In line, T2D or CON subjects with steatosis featured lower ICMMT than those without steatosis (both P < 0.05).Insulin clearance is reduced in both T1D and T2D within the first year after diagnosis but correlates negatively with liver lipid content rather in T2D. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity in each diabetes type, which may suggest specific mechanisms affecting insulin kinetics.
Randomized Trial of the Insulin-Only iLet Bionic Pancreas for the Treatment of Cystic Fibrosis– Related Diabetes
Authors: Jordan S. Sherwood, Luz E. Castellanos, Mollie Y. O’Connor, Courtney A. Balliro, Mallory A. Hillard, Sarah Grace Gaston, Rachel Bartholomew, Evelyn Greaux, Amy Sabean, Hui Zheng, Peter Marchetti, Ahmet Uluer, Gregory S. Sawicki, Isabel Neuringer, Firas H. El-Khatib, Edward R. Damiano, Steven J. Russell, Melissa S. Putman
Journal: Diabetes Care (2023)

OBJECTIVE Cystic fibrosis–related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial. RESEARCH DESIGN AND METHODS Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC). No restrictions were placed on diet or activity. The primary outcome was the percent time sensor-measured glucose was in target range 70–180 mg/dL (time in range [TIR]) on days 3–14 of each arm, and key secondary outcomes included mean continuous glucose monitoring (CGM) glucose and the percent time sensor-measured glucose was in hypoglycemic range &amp;lt;54 mg/dL. RESULTS TIR was significantly higher in the BP arm than the UC arm (75 ± 11% vs. 62 ± 22%, P = 0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150 ± 19 vs. 171 ± 45 mg/dL, P = 0.007). There was no significant difference in percent time with sensor-measured glucose &amp;lt;54 mg/dL (0.27% vs. 0.36%, P = 1.0), although self-reported symptomatic hypoglycemia episodes were higher during the BP arm than the UC arm (0.7 vs. 0.4 median episodes per day, P = 0.01). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either arm. CONCLUSIONS Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting that this may be an important therapeutic option for this patient population.
The Mortality Burden of Untreated Aortic Stenosis
Authors: Philippe Généreux, Rahul P. Sharma, Robert J. Cubeddu, Lucy Aaron, Omar M. Abdelfattah, Konstantinos P. Koulogiannis, Leo Marcoff, Mostafa Naguib, Samir R. Kapadia, Rajendra R. Makkar, Vinod H. Thourani, Benjamin S. van Boxtel, David J. Cohen, Michael Dobbles, Glenn R. Barnhart, Michelle Kwon, Philippe Pibarot, Martin B. Leon, Linda D. Gillam
Journal: Journal of the American College of Cardiology (2023)

The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or severe, per echocardiogram, and recommend aortic valve replacement (AVR) when the AS is severe. The authors sought to describe mortality rates across the entire spectrum of untreated AS from a contemporary, large, real-world database. We analyzed a deidentified real-world data set including 1,669,536 echocardiographic reports (1,085,850 patients) from 24 U.S. hospitals (egnite Database, egnite). Patients >18 years of age were classified by diagnosed AS severity. Untreated mortality and treatment rates were examined with Kaplan-Meier (KM) estimates, with results compared using the log-rank test. Multivariate hazards analysis was performed to assess associations with all-cause mortality. Among 595,120 patients with available AS severity assessment, the KM-estimated 4-year unadjusted, untreated, all-cause mortality associated with AS diagnosis of none, mild, mild-to-moderate, moderate, moderate-to-severe, or severe was 13.5% (95% CI: 13.3%-13.7%), 25.0% (95% CI: 23.8%-26.1%), 29.7% (95% CI: 26.8%-32.5%), 33.5% (95% CI: 31.0%-35.8%), 45.7% (95% CI: 37.4%-52.8%), and 44.9% (95% CI: 39.9%-49.6%), respectively. Results were similar when adjusted for informative censoring caused by treatment. KM-estimated 4-year observed treatment rates were 0.2% (95% CI: 0.2%-0.2%), 1.0% (95% CI: 0.7%-1.3%), 4.2% (95% CI: 2.0%-6.3%), 11.4% (95% CI: 9.5%-13.3%), 36.7% (95% CI: 31.8%-41.2%), and 60.7% (95% CI: 58.0%-63.3%), respectively. After adjustment, all degrees of AS severity were associated with increased mortality. Patients with AS have high mortality risk across all levels of untreated AS severity. Aortic valve replacement rates remain low for patients with severe AS, suggesting that more research is needed to understand barriers to diagnosis and appropriate approach and timing for aortic valve replacement.
Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study
Journal: BMJ (2023)

Main outcome measures:The second sentence should state: Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at "five and 10 years" using pseudo values. Results:The third sentence should state: Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of "0.843 (95% confidence interval 0.841 to 0.844) and 0.833 (0.831 to 0.835)" at five and 10 years, respectively.
A systematic review on adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in individuals with mild cognitive impairment and Alzheimer's disease dementia
Authors: Cerys Oliver, Haoxuan Li, Bijetri Biswas, David Woodstoke, Jonathan Blackman, Anneka Butters, Cheney Drew, Victoria Gabb, Sam Harding, Camilla M. Hoyos, Adrian Kendrick, Sarah Rudd, Nicholas Turner, Elizabeth Coulthard
Journal: Sleep Medicine Reviews (2023)

Obstructive sleep apnoea (OSA) is highly prevalent in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The gold standard treatment for OSA is continuous positive airway pressure (CPAP). Long-term, well-powered efficacy trials are required to understand whether CPAP could slow cognitive decline in individuals with MCI/AD, but its tolerability in this group remains uncertain. The present review investigates CPAP adherence among individuals with OSA and MCI/AD. Electronic searches were performed on 8 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Six independent studies and four secondary analyses included 278 unique participants (mean age = 72.1 years). In five of the retained studies, around half of participants (45% N = 85 MCI, 56% N = 22 AD) were adherent to CPAP, where ≥4 h use per night was considered adherent. Three of the retained studies also reported average CPAP use to range between 3.2 and 6.3 h/night. CPAP adherence in individuals with MCI and AD is low, albeit similar to the general elderly population. Reporting adherence in future studies as both average duration as well as using a binary cut-off would improve our understanding of the optimum CPAP use in dementia clinical trials and care.
Multiple long-term conditions in people with psoriasis: a latent class and bidirectional Mendelian randomization analysis
Authors: Christos V Chalitsios, Devendra Meena, Maria Manou, Christos Papagiannopoulos, Georgios Markozannes, Dipender Gill, Bowen Su, Konstantinos K Tsilidis, Evangelos Evangelou, Ioanna Tzoulaki
Journal: British Journal of Dermatology (2023)

Abstract Background Coexisting long-term conditions (LTCs) in psoriasis and their potential causal associations with the disease are not well ­established. Objectives To determine distinct clusters of LTCs in people with psoriasis and the potential bidirectional causal association between these LTCs and psoriasis. Methods Using latent class analysis, cross-sectional data from people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related comorbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTCs. Two-sample bidirectional Mendelian randomization (MR) analysis assessed the potential causal direction using independent genetic variants that reached genome-wide significance (P &amp;lt; 5 × 10–8). Results Five comorbidity clusters were identified in a population of 10 873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure [genetic correlation (rg) = 0.23, P = 8.8 × 10−8], depression (rg = 0.12, P = 2.7 × 10−5), coronary artery disease (CAD; rg = 0.15, P = 2 × 10−4) and type 2 diabetes (rg = 0.19, P = 3 × 10−3). Genetic liability to CAD was associated with an increased risk of psoriasis [inverse variance weighted (IVW) odds ratio (ORIVW) 1.159, 95% confidence interval (CI) 1.055–1.274; P = 2 × 10−3]. The MR pleiotropy residual sum and outlier (MR-PRESSO; ORMR-PRESSO 1.13, 95% CI 1.042–1.228; P = 6 × 10−3) and the MR-robust adjusted profile score (RAPS) (ORMR-RAPS 1.149, 95% CI 1.062–1.242; P = 5 × 10−4) approaches corroborate the IVW findings. The weighted median (WM) generated similar and consistent effect estimates but was not statistically significant (ORWM 1.076, 95% CI 0.949–1.221; P = 0.25). Evidence for a suggestive increased risk was detected for CAD (ORIVW 1.031, 95% CI 1.003–1.059; P = 0.03) and heart failure (ORIVW 1.019, 95% CI 1.005–1.033; P = 9 × 10−3) in those with a genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance. Conclusions Five distinct clusters of psoriasis comorbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Coexisting LTCs share with psoriasis common genetic and nongenetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted CAD is possibly associated with an increased risk of psoriasis, altering our prior knowledge.
Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy
Authors: Gloria Iacoboni, Víctor Navarro, Ana África Martín-López, Kai Rejeski, Mi Kwon, Katarzyna Aleksandra Jalowiec, Paula Amat, Juan Luis Reguera-Ortega, Laura Gallur, Viktoria Blumenberg, Sara Gutiérrez-Herrero, Claire Roddie, Ana Benzaquén, Javier Delgado-Serrano, Mario Andrés Sánchez-Salinas, Rebeca Bailén, Cecilia Carpio, Lucia López-Corral, Rafael Hernani, Mariana Bastos, Maeve O'Reilly, Lourdes Martín-Martín, Marion Subklewe, Pere Barba
Journal: Journal of Clinical Oncology (2023)

Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure.
Elderly male patients with hidradenitis suppurativa have more severe disease independent of disease duration
Authors: Valdemar Wendelboe Nielsen, Hans Christian Ring, Nikolaj Holgersen, Simon Francis Thomsen
Journal: British Journal of Dermatology (2023)

The recent study by van der Weijden et al. proposed defining hidradenitis suppurativa (HS) in the elderly (&amp;gt; 60 years of age) as ‘HS tarda’. We verify and extend the findings by van der Weijden et al. by demonstrating that variation in HS severity is explained to an increasing extent by sex with increasing age, but is independent of overall disease duration, and that HS in the elderly shows significant variation in age of onset and body area involvement. This supports the idea that HS activity varies between different age groups, but the relationship remains more complex than a binary definition.
Conjunctival Spindle Cell/Sclerosing Rhabdomyosarcoma
Authors: Yi-Wen Su, Lei-Chi Wang, Nai-Wen Fan
Journal: Ophthalmology (2023)

A 13-year-old Asian boy had a fast-growing solid mass on his right lower palpebral conjunctiva and medial canthus for 1 month (A). Magnetic resonance imaging revealed 2 masses in the medial and inferior orbit. Histopathology of the conjunctival tumor showed ovoid and spindled cells with hyperchromatic nuclei and abundant eosinophilic cytoplasm, arranged in a fascicular pattern within hyalinized stroma (arrowheads). Some exhibited a pseudovascular pattern (B, arrows). Immunohistochemical staining results were positive for desman (C) and MyoD1 (D). Molecular analysis revealed an absence of the PAX3/FOXO1 fusion gene. The boy was diagnosed with spindle cell/sclerosing rhabdomyosarcoma and received concurrent chemotherapy. (Magnified version of Figure A-D is available online at www.aaojournal.org).
Incidence, mortality and survival of Merkel cell carcinoma: a systematic review of population-based studies
Authors: Samiha T Mohsen, Emma L Price, An-Wen Chan, Timothy P Hanna, James J Limacher, Carolyn Nessim, Jessica E Shiers, Victor Tron, Frances C Wright, Aaron M Drucker
Journal: British Journal of Dermatology (2023)

Abstract Background Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that most commonly occurs in ultraviolet-exposed body sites. The epidemiology of MCC in different geographies and populations is not well characterized. Objectives The objective of this systematic review is to summarize evidence on the incidence, mortality and survival rates of MCC from population-based studies. Methods We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from database inception to 6 June 2023. No geographic, age or date exclusions were applied. We included population-based studies of MCC that reported the incidence, survival or mortality rate, and also considered systematic reviews. A data-charting form was created and validated to identify variables to extract. Two reviewers then independently charted the data for each included study with patient characteristics, and estimates of incidence rate, mortality rate, and survival rate and assessed the quality of included studies using the Joanna Briggs Institute Checklist for Prevalence studies, Newcastle–Ottawa Scale and Assessment of Multiple Systematic Reviews. We abstracted age-, sex-, stage- and race-stratified outcomes, and synthesized comparisons between strata narratively and using vote counting. We assessed the certainty of evidence for those comparisons using the Grading of Recommendations, Assessments, Developments and Evaluations framework. Results We identified 11 472 citations, of which 52 studies from 24 countries met our inclusion criteria. Stage I and the head and neck were the most frequently reported stage and location at diagnosis. The incidence of MCC is increasing over time (high certainty), with the highest reported incidences reported in southern hemisphere countries [Australia (2.5 per 100 000); New Zealand (0.96 per 100 000) (high certainty)]. Male patients generally had higher incidence rates compared with female patients (high certainty), although there were some variations over time periods. Survival rates varied, with lower survival and/or higher mortality associated with male sex (moderate certainty), higher stage at diagnosis (moderate-to-high certainty), older age (moderate certainty), and immunosuppression (low-to-moderate certainty). Conclusions MCC is increasing in incidence and may increase further given the ageing population of many countries. The prognosis of MCC is poor, particularly for male patients, those who are immunosuppressed, and patients diagnosed at higher stages or at an older age.
Concomitant Left Atrial Appendage Occlusion and Transcatheter Aortic Valve Replacement Among Patients With Atrial Fibrillation
Authors: Samir R. Kapadia, Amar Krishnaswamy, Brian Whisenant, Srinivasa Potluri, Vijay Iyer, Joseph Aragon, Philip Gideon, Justin Strote, Robert Leonardi, Himanshu Agarwal, German Larrain, Carlos Sanchez, Sidakpal S. Panaich, James Harvey, Torsten Vahl, Venu Menon, Kathy Wolski, Qiuqing Wang, Martin B. Leon
Journal: Circulation (2023)

Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) and is associated with increased risk of bleeding and stroke. While left atrial appendage occlusion (LAAO) is approved as an alternative to anticoagulants for stroke prevention in patients with AF, placement of these devices in patients with severe aortic stenosis, or when performed at the same time as TAVR, has not been extensively studied.
Associations Between Social Determinants of Health and Cardiovascular Health of U.S. Adult Cancer Survivors
Authors: Danish Iltaf Satti, Jeffrey Shi Kai Chan, Edward Christopher Dee, Yan Hiu Athena Lee, Abraham Ka Chung Wai, Sourbha S. Dani, Salim S. Virani, Michael D. Shapiro, Garima Sharma, Tong Liu, Gary Tse
Journal: JACC CardioOncology (2023)

Relationships between the social determinants of health (SDOH) and cardiovascular health (CVH) of cancer survivors are underexplored. The study sought to investigate associations between the SDOH and CVH of adult cancer survivors. Data from the U.S. National Health Interview Survey (2013-2017) were used. Participants reporting a history of cancer were included, excluding those with only nonmelanotic skin cancer, or with missing data for any domain of SDOH or CVH. SDOH was quantified with a 6-domain, 38-item score, consistent with the Centers for Disease Control and Prevention recommendations (higher score indicated worse deprivation). CVH was quantified based on the American Heart Association's Life's Essential 8, but due to unavailable detailed dietary data, a 7-item CVH score was used, with a higher score indicating worse CVH. Survey-specific multivariable Poisson regression was used to test associations between SDOH quartiles and CVH. Altogether, 8,254 subjects were analyzed, representing a population of 10,887,989 persons. Worse SDOH was associated with worse CVH (highest vs lowest quartile: risk ratio 1.30; 95% CI: 1.25-1.35; P < 0.001), with a grossly linear relationship between SDOH and CVH scores. Subgroup analysis found significantly stronger associations in younger participants (Pinteraction = 0.026) or women (Pinteraction = 0.001) but without significant interactions with race (Pinteraction = 0.051). Higher scores in all domains of SDOH were independently associated with worse CVH (all P < 0.001). Higher SDOH scores were also independently associated with each component of the CVH score (all P < 0.05 for highest SDOH quartile). An unfavorable SDOH profile was independently associated with worse CVH among adult cancer survivors in the United States.
4-Year Outcomes of Patients With Aortic Stenosis in the Evolut Low Risk Trial
Authors: John K. Forrest, G. Michael Deeb, Steven J. Yakubov, Hemal Gada, Mubashir A. Mumtaz, Basel Ramlawi, Tanvir Bajwa, Paul S. Teirstein, Didier Tchétché, Jian Huang, Michael J. Reardon
Journal: Journal of the American College of Cardiology (2023)
Immediate smoking cessation support during lung cancer screening: long-term outcomes from two randomised controlled trials
Authors: Parris J Williams, Keir E J Philip, Sara C Buttery, Alexis Perkins, Ley Chan, Emily C Bartlett, Anand Devaraj, Samuel V Kemp, James Addis, Jane Derbyshire, Michelle Chen, Michael I Polkey, Anthony A Laverty, Nicholas S Hopkinson
Journal: Thorax (2023)

Background Immediate smoking cessation interventions delivered alongside targeted lung health checks (TLHCs) to screen for lung cancer increase self-reported abstinence at 3 months. The impact on longer term, objectively confirmed quit rates remains to be established. Methods We followed up participants from two clinical trials in people aged 55–75 years who smoked and took part in a TLHC. These randomised participants in the TLHC by day of attendance to either usual care (UC) (signposting to smoking cessation services) or an offer of immediate smoking cessation support including pharmacotherapy. In the QuLIT1 trial, this was delivered face to face and in QuLIT2, it was delivered remotely. Follow-up was conducted 12 months after the TLHC by telephone interview with subsequent biochemical verification of smoking cessation using exhaled CO. Results 430 people were enrolled initially (115 in QuLIT1 and 315 in QuLIT2), with 4 deaths before 12 months leaving 426 (62.1±5.27 years old and 48% women) participants for analysis. At 12 months, those randomised to attend on smoking cessation support intervention days had higher quit rates compared with UC adjusted for age, gender, deprivation, and which trial they had been in; self-reported 7-day point prevalence (20.0% vs 12.8%; adjusted OR (AOR)=1.78; 95% CI 1.04 to 2.89) and CO-verified quits (12.1% vs 4.7%; AOR=2.97; 95% CI 1.38 to 6.90). Those in the intervention arm were also more likely to report having made a quit attempt (30.2% vs UC 18.5%; AOR 1.90; 95% CI 1.15 to 3.15). Conclusion Providing immediate smoking cessation support alongside TLHC increases long term, biochemically confirmed smoking abstinence. Trial registration number ISRCTN12455871 .
Prevalence of clinically meaningful antiphospholipid antibodies in patients with systemic lupus erythematosus varies by race and ethnicity
Authors: Cécile M Yelnik, Xianhong Xie, Marta M Guerra, Nathalie Costedoat-Chalumeau, Arezou Khosroshahi, Diane L Kamen, Noa Schwartz, Patricia Katz, Margaret Minett, R Toby Amoss, April Fu, Gaëlle Guettrot-Imbert, Estibaliz Lazaro, Véronique Le Guern, Jim Oates, Maria Dall'Era, Jinoos Yazdany, Anna Molto, Mimi Y Kim, Jane E Salmon
Journal: Annals of the Rheumatic Diseases (2023)